Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway

2021 ◽  
pp. 1-14
Author(s):  
Guangmang Liu ◽  
Jie Zheng ◽  
Ke Gu ◽  
Caimei Wu ◽  
Gang Jia ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Tai-yu Zhai ◽  
Bao-hong Cui ◽  
Lei Zou ◽  
Jing-ya Zeng ◽  
Song Gao ◽  
...  

The calcium-sensing receptors (CaSRs) play an important role in many tissues and organs that are involved in inflammatory reactions. Peripheral blood polymorphonuclear neutrophils (PMNs) are important inflammatory cells. However, the expression and functions of CaSR in peripheral blood PMNs are still not reported. In this study, we collected rat peripheral blood PMNs to observe the relationship between CaSR and PMNs. From the results, we found first that the CaSR protein was expressed in PMNs, and it increased after PMNs were activated with fMLP. In addition, CaSR activator cincalcet promoted the expression of CaSR and P-p65 (NF-κB signaling pathway protein) and Bcl-xl (antiapoptosis protein), and it increased the secretion of interleukin-6 (IL-6) and myeloperoxidase (MPO); meanwhile, it decreased proapoptosis protein Bax expression and the production of IL-10 and reactive oxygen species (ROS). At the same time, cincalcet also decreased the PMN apoptosis rate analyzed by flow cytometry. However, CaSR inhibitor NPS-2143 and NF-κB signaling pathway inhibitor PDTC reverse the results cited earlier. All of these results indicated that CaSR can regulate PMN functions and status to play a role in inflammation, which is probably through the NF-κB signaling pathway.


2018 ◽  
Vol 34 ◽  
pp. 87-93 ◽  
Author(s):  
Shumei Wang ◽  
Liyun Qiu ◽  
Haiyan Song ◽  
Ningning Dang

Melanoma is a common and aggressive skin cancer caused by the oncogenic transformation of melanocytes. NPS-2143 (hydrochloride) is a calcification drug that acts as an antagonist of the calcium-sensing receptor (CaSR) and consequently stimulates the release of parathyroid hormone. In the present work, we treated cells from the human melanoma cell line M14 to investigate the effects of NPS-2143 on melanoma cells and elucidate their underlying mechanisms. We observed that NPS-2143 inhibits the survival and proliferation of M14 cells and suppresses the migration and proliferation of M14 cells by inducing apoptosis. The Bax/Bcl‑2 ratio in M14 cells was enhanced by the NPS-2143 treatment, suggesting that the mitochondrial apoptotic pathway was activated. The expression and phosphorylation of proteins involved in the PI3K signaling pathway were altered by NPS-2143 treatment. Our data show that NPS-2143 impacts the viability and induces the apoptosis of melanoma M14 cells through its impact on the PI3K signaling pathway. It suggests that NPS-2143 could represent a promising candidate for melanoma treatment.


Author(s):  
Lennis Beatriz Orduña-Castillo ◽  
Jorge Eduardo del-Río-Robles ◽  
Irving García-Jiménez ◽  
César Zavala-Barrera ◽  
Yarely Mabell Beltrán-Navarro ◽  
...  

2016 ◽  
Vol 377 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Bo Tang ◽  
Jimmy Y.C. Chow ◽  
Tobias Xiao Dong ◽  
Shi-Ming Yang ◽  
De-Sheng Lu ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jingjing Ye ◽  
Wei Ai ◽  
Fenglin Zhang ◽  
Xiaotong Zhu ◽  
Gang Shu ◽  
...  

Porcine bone marrow mesenchymal stem cells (pBMSCs) have the potential for application in regenerative medicine. This study aims to investigate the effects of extracellular calcium (Ca2+o) on pBMSCs proliferation and to explore the possible underlying mechanisms. The results demonstrated that 4 mMCa2+osignificantly promoted pBMSCs proliferation by reducing the G0/G1 phase cell percentage and by increasing the S phase cell proportion and the proliferation index of pBMSCs. Accordingly,Ca2+ostimulated the expression levels of proliferative genes such as cyclin A2, cyclin D1/3, cyclin E2, and PCNA and inhibited the expression of p21. In addition,Ca2+oresulted in a significant elevation of intracellular calcium and an increased ratio of p-ERK/ERK. However, inhibition of calcium-sensing receptor (CaSR) by its antagonist NPS2143 abolished the aforementioned effects ofCa2+o. Moreover,Ca2+o-induced promotion of pBMSCs proliferation, the changes of proliferative genes expression levels, and the activation of ERK1/2 signaling pathway were effectively blocked by U0126, a selective ERK kinase inhibitor. In conclusion, our findings provided evidence that the enhanced pBMSCs proliferation in response toCa2+owas associated with the activation of CaSR and ERK1/2 signaling pathway, which may be useful for the application of pBMSCs in future clinical studies aimed at tissue regeneration and repair.


Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 69 ◽  
Author(s):  
Gordon L. Klein

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.


2018 ◽  
Vol 24 ◽  
pp. 130-131
Author(s):  
Pratibha Abraham ◽  
Muhammad Siddiqui ◽  
Deepashree Gupta ◽  
Stewart Albert

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